Q8CHX6 (MBTP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Membrane-bound transcription factor site-2 protease
EC=3.4.24.85

Alternative name(s):
Endopeptidase S2P

Gene names

Name:

Mbtps2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	515 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Intramembrane proteolysis of sterol-regulatory element-binding proteins (SREBPs) within the first transmembrane segment thereby releasing the N-terminal segment with a portion of the transmembrane segment attached. Site-2 cleavage comes after site-1 cleavage which takes place in the lumenal loop By similarity.
Catalytic activity	Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2 is cleaved at the site 477-DRSRILL-|-CVLTFLCLSFNPLTSLLQWGGA-505. The residues Asn-Pro, 11 residues distal to the site of cleavage in the membrane-spanning domain, are important for cleavage by S2P endopeptidase. Replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Membrane; Multi-pass membrane protein Probable. Cytoplasm By similarity.
Sequence similarities	Belongs to the peptidase M50A family.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism
Cellular component	Cytoplasm Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cholesterol metabolic process Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 515	515	Membrane-bound transcription factor site-2 protease		PRO_0000261592
Regions
	Topological domain	1 – 3	3	Cytoplasmic By similarity
	Transmembrane	4 – 24	21	Helical; Potential
	Topological domain	25 – 74	50	Lumenal By similarity
	Transmembrane	75 – 95	21	Helical; Potential
	Transmembrane	96 – 107	12	Helical; Potential
	Topological domain	108 – 140	33	Lumenal By similarity
	Transmembrane	141 – 165	25	Helical; Potential
	Transmembrane	170 – 182	13	Helical; Potential
	Transmembrane	183 – 205	23	Helical; Potential
	Transmembrane	225 – 247	23	Helical; Potential
	Topological domain	248 – 442	195	Lumenal By similarity
	Transmembrane	443 – 460	18	Helical; Potential
	Transmembrane	461 – 472	12	Helical; Potential
	Topological domain	473 – 488	16	Lumenal Potential
	Transmembrane	489 – 509	21	Helical; Potential
	Topological domain	510 – 515	6	Cytoplasmic Potential
	Compositional bias	114 – 132	19	Poly-Ser
	Compositional bias	281 – 382	102	Cys-rich
Sites
	Active site	168	1	By similarity
	Metal binding	167	1	Zinc; catalytic By similarity
	Metal binding	171	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	333	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	Q8CHX6 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: E7C3A93A58D17A21	FASTA	515	56,960
	10 20 30 40 50 60 MIPVSLLVVV VGGWTAVYLA DLVLKSSVYF KHSYEDWLEN NGLSISPFHI RWQTSIFNRA 70 80 90 100 110 120 FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLMQ TLAQMMADSP SPYSSSSSSS 130 140 150 160 170 180 SSSSSSSSSS SSLHNEQVLQ VVVPGINLPV NQLTYFFAAV LISGVVHEIG HGIAAIREQV 190 200 210 220 230 240 RFNGFGIFLF IIYPGAFVDL FTTHLQLISP VQQLRIFCAG IWHNFVLALL GILALVLLPV 250 260 270 280 290 300 ILLPFYYTGV GVLITEVAED SPAIGPRGLF VGDLVTHLQD CPVTNVQDWN ECLDTIAYEP 310 320 330 340 350 360 QIGYCISAST LQQLSFPVRA YKRLDGSTEC CNNHSLTDVC FSYRNNFNKR LHTCLPARKA 370 380 390 400 410 420 VEATQVCRSN KDCKSGASSS FCIVPSLETH TRLIKVKHPP QIDMLYVGHP LHLHYTVSIT 430 440 450 460 470 480 SFIPRFNFLS IDLPVIVETF VKYLISLSGA LAIVNAVPCF ALDGQWILNS FLDATLTSVI 490 500 510 GDNDVKDLIG FFILLGGSVL LAANVTLGLW MVTAR

References

[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Heart.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary tumor.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK148325 mRNA. Translation: BAE28482.1. AK164486 mRNA. Translation: BAE37807.1. AL663072 Genomic DNA. Translation: CAM18093.1. BC038343 mRNA. Translation: AAH38343.1.
IPI	IPI00229772.
RefSeq	NP_758511.1. NM_172307.3.
UniGene	Mm.37577.
3D structure databases
ProteinModelPortal	Q8CHX6.
SMR	Q8CHX6. Positions 157-234, 249-294.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8CHX6.
Protein family/group databases
MEROPS	M50.001.
Proteomic databases
PRIDE	Q8CHX6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000058098; ENSMUSP00000059471; ENSMUSG00000046873.
GeneID	270669.
KEGG	mmu:270669.
NMPDR	fig|10090.3.peg.22376.
UCSC	uc009usb.1. mouse.
Organism-specific databases
CTD	51360.
MGI	MGI:2444506. Mbtps2.
Phylogenomic databases
GeneTree	ENSGT00510000048066.
HOVERGEN	HBG006397.
OMA	SLENQTR.
Gene expression databases
ArrayExpress	Q8CHX6.
Bgee	Q8CHX6.
Genevestigator	Q8CHX6.
GermOnline	ENSMUSG00000046873. Mus musculus.
Family and domain databases
InterPro	IPR001193. Pept_M50_SREBP. IPR008915. Peptidase_M50. [Graphical view]
KO	K07765.
Pfam	PF02163. Peptidase_M50. 1 hit. [Graphical view]
PRINTS	PR01000. SREBPS2PTASE.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	393364.
SOURCE	Search...

Entry information

Entry name

MBTP2_MOUSE

Accession

Primary (citable) accession number: Q8CHX6
Secondary accession number(s): A2AC85

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	March 1, 2003
Last modified:	November 16, 2011
This is version 71 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program